The present application is the continuation of an ongoing program of research aimed at developing an animal model of endolymphatic hydrops in the rabbit. A major goal of this work has been to describe functional changes in the rabbit model including elevations in hearing threshold and reduced amplitudes for acoustic distortion products. These functional changes, then have been routinely related to the corresponding histopathology. Similarities between functional losses in the rabbit model and those described for patients with Meniere's disease have served to validate this research approach. Results, to date, indicate that the rabbit may provide one of the most suitable models of endolymphatic hydrops. Thus, we have demonstrated that the rabbit exhibits a low-frequency hearing loss and, under certain circumstances, the hearing deficit is accompanied by severe vestibular disturbances. The goals of the experiments proposed in the present application are to further investigate the processes which induce vestibular upset by manipulating the type of damage produced to the endolymphatic sac and duct. The results of these experiments will help elucidate the role of vascular disturbances in contrast to that of increased endolymphatic pressure alone. The rabbit model will also be studied to determine its responsiveness to osmotic and diuretic agents which should help in clarifying the role of increased endolymphatic pressure with respect to that involving ionic or metabolic imbalances. Finally, behavioral and single cochlear nerve-fiber studies will attempt to determine if deterioration in frequency selectivity is one of the more sensitive indicators of developing endolymphatic hydrops, since a breakdown in this specific mechanism is one of the major functional symptoms in early Meniere's disease.
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